We will investigate the biological properties of molecules labeled using bifunctional chelates, with the aim of developing clinically useful tumor localizing agents. Bleomycin will be labeled by attaching metal chelating groups to the "terminal amine group", a site not critical for cellular transport. The first compound of this type (BLEDTA) has been prepared, and has been found to mimic the biodistribuion of bleomycin. When radioactive metal ions are added in carrier-free solutions to "kits" containing these previously modified molecules, extremely stable complexes should form immediately. In-111, Tc-99m, Ga-68 and Fe-55 will be used to prepare radiopharmaceuticals with high specific activity (greater than 100 Ci/m mol) so that maximum binding to tumor cell receptors can be achieved. New derivatives, and isomers of non-radioactive cobalt and chromimum bleomycin, containing new bifunctional chelates of varying structure and charge will be studied as well as conjugates of anti-CEA IgG antibody and transferrin. Competitive inhibition of binding of BLEDTA, and other conjugates to tumor cells in vitro will be studied. Binding kinetics will be correlated with high resolution E.M. radioautography in order to investigate the possible existence of receptor sites on the cells. New compounds will be studied in a KHJJ mouse tumor model, as well as in a mouse brain tumor metastasis model using both tissue assay and radioautography. We also plan to study the therapeutic effectiveness of BLEDTA derivatives uing the bleomycin molecule as a vehicle for transporting anti-tumor functional groups such as Fe (II) chelates which produce free radicals, or high cross section metal atoms for neutron capture such as U-235, specifically into tumor cells, possibly into close physical contact with DNA. The best derivative as judged from the in vitro and animal experiments will be investigated as tumor imaging agents in selected cancer patients.